目的:新生儿脑病(NE)是一种神经系统综合征,表现为严重的神经系统损害和并发症。缺氧缺血性脑病是导致不良预后的主要因素,负责50%-80%的新生儿重症监护病房入院。然而,一些伴有缺氧性脑损伤的NE病例不能完全归因于缺氧缺血。我们旨在确定可能与伴有缺氧性脑损伤而不是缺氧缺血的NE病例相关的多种致病遗传变异。
方法:我们收集了34例诊断为NE并伴有缺氧性脑损伤的患者10年的数据。有以下具体情况的患者被排除:1)早产(<32周),2)无缺氧事件史,3)相关异常,4)新生儿感染,5)产前或围产期产科并发症,6)由于其他医疗条件造成的严重缺氧,7)早期死亡(1周内)。对临床和放射学特征进行了全面审查。
结果:对11例(32.4%)患者进行了基因诊断,在以下9个基因中鉴定出致病性变异:CACNA1A(n=2),KCNQ2(n=2),SCN2A(n=1),SCN8A(n=1),STXBP1(n=1),NSD1(n=1),PURA(n=1),ZBTB20(n=1),和ENG(n=1)。除早产外,没有特定的治疗结果或临床特征与遗传分析结果相关。根据基因测试的结果尝试个性化治疗,例如在KCNQ2或SCN8A变体患者中施用钠通道阻滞剂,以及在STXBP1或SCN2A突变患者中实施生酮饮食,在这些患者中证明了一定程度的有效性。
结论:遗传分析可能有助于诊断NE和并发缺氧性脑损伤的潜在病因,与最初的临床特征无关。
OBJECTIVE: Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia.
METHODS: We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted.
RESULTS: A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: CACNA1A (n=2), KCNQ2 (n=2), SCN2A (n=1), SCN8A (n=1), STXBP1 (n=1), NSD1 (n=1), PURA (n=1), ZBTB20 (n=1), and ENG (n=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with KCNQ2 or SCN8A variants and the implementation of a ketogenic diet in patients with STXBP1 or SCN2A mutations, which demonstrated some degree of effectiveness in these patients.
CONCLUSIONS: Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.